-
Frontiers in Cardiovascular Medicine 2022The clinical benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for preventing and treating cardiovascular events remains controversial. We aimed to study the...
BACKGROUND
The clinical benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for preventing and treating cardiovascular events remains controversial. We aimed to study the effect of SGLT2 inhibitors on cardiovascular outcomes and safety events, giving particular attention to the benefits in subgroups of patients with different diseases.
METHOD
Randomized controlled trials (RCTs) reporting cardiovascular outcomes following the administration of SGLT2 inhibitors and placebo were included in this study. Cardiovascular outcomes included all-cause death, major adverse cardiovascular events (MACEs), cardiovascular (CV) death, myocardial infarction (MI), stroke, and hospitalization for heart failure (HHF). We also focused on the cardiovascular benefits of SGLT2 inhibitor application in subgroups of patients with different diseases, including type 2 diabetes (T2D), heart failure (HF), high risk of atherosclerotic cardiovascular disease (ACD), diagnosed ACD, and chronic kidney disease (CKD). Safety events associated with SGLT2 inhibitors, including acute kidney injury (AKI), diabetic ketoacidosis (DKA), hypoglycemia, urinary tract infection, thromboembolic event, bone fracture, volume depletion, and amputation, were also reported.
RESULTS
This meta-analysis included 15 RCTs with 78,212 participants. SGLT2 inhibitors reduced the risk of all-cause death (RR 0.89; 95% CI: 0.85-0.94; I2 = 32%; < 0.01), CV death (RR 0.87; 95% CI: 0.82-0.93; I2 = 11%; < 0.01), MACEs (RR 0.89; 95% CI: 0.84-0.94; I2 = 46%; < 0.01), HHF (RR 0.70; 95% CI: 0.66-0.74; I2 = 0%; < 0.01), and AKI (RR 0.81; 95% CI: 0.73-0.90; I2 = 0%; < 0.01) but increased the risk of DKA (RR 2.56; 95% CI: 1.72-3.80; I2 = 0%; < 0.01). However, no apparent benefit in MI and stroke was observed between the SGLT2 inhibitor and control groups. SGLT2 inhibitors reduced the risk of all-cause death, MACEs, CV death, and HHF in diabetic patients; reduced the risk of all-cause death, MACEs, CV death, MI, and HHF in primary prevention; reduced the risk of all-cause death, CV death, and HHF in patients with ACD and HF; and reduced the risk of MACEs, CV death, and HHF in patients with CKD.
CONCLUSION
SGLT2 inhibitors have a positive effect in reducing the risk of all-cause death, CV death, MACE, HHF, and AKI and increasing the risk of DKA. The application of SGLT2 inhibitors in the primary prevention of ACD also has certain clinical benefits in reducing MI.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022306490].
PubMed: 36312269
DOI: 10.3389/fcvm.2022.926979 -
BMJ Open Oct 2022To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes. (Meta-Analysis)
Meta-Analysis
Cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients without diabetes: a systematic review and meta-analysis of randomised placebo-controlled trials.
OBJECTIVES
To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes.
METHODS
We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17 August 2022. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Random-effects meta-analyses were performed to pool effect measures across studies. Risk ratios (RRs) with 95% CIs are expressed for composite cardiovascular outcome of cardiovascular death or hospitalisation for heart failure, cardiovascular death, hospitalisation for heart failure, all-cause mortality and composite renal outcome of ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease or renal death. Annual rate of change in eGFR is expressed as the mean difference with 95% CI.
RESULTS
We identified four trials with 8927 patients with heart failure or chronic kidney disease (CKD). Compared with placebo, SGLT2 inhibitors showed favourable effects on the composite cardiovascular outcome (RR: 0.79, 95% CI: 0.71 to 0.87; moderate certainty), cardiovascular death (0.85, 0.74 to 0.99; moderate certainty), hospitalisation for heart failure (0.72, 0.62 to 0.82; moderate certainty), the composite renal outcome (0.64, 0.48 to 0.85; low certainty) and the annual rate of change in eGFR (mean difference: 0.99, 0.59 to 1.39 mL/min/1.73 m/year; moderate certainty), while there was no significant difference in all-cause mortality (0.88, 0.77 to 1.01; very low certainty). Moderate certainty evidence indicated that SGLT2 inhibitors reduced the risk of serious adverse events and acute renal failure. Low certainty evidence suggested that SGLT2 inhibitors increased the risk of urinary tract infection and genital infection, while there were no differences in discontinuation due to adverse events, amputation, fracture, hypoglycaemia, ketoacidosis or volume depletion.
CONCLUSIONS
Evidence of low to moderate certainty suggests that SGLT2 inhibitors provide cardiorenal benefits but have increased risk for urinary tract infection and genital infection in patients without diabetes and with heart failure or CKD.
PROSPERO REGISTRATION NUMBER
CRD42021239807.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glucose; Heart Failure; Humans; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Sodium; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 36241355
DOI: 10.1136/bmjopen-2021-060655 -
Frontiers in Endocrinology 2022Diabetes mellitus (DM) is a global health problem, and it has become a shocking threat in the contemporary era. The objective of this study was to analyze the safety of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetes mellitus (DM) is a global health problem, and it has become a shocking threat in the contemporary era. The objective of this study was to analyze the safety of sotagliflozin in patients with DM systematically and intuitively.
METHODS
On November 15, 2021, literature retrieval was performed on PubMed, Web of Science, EBSCO, and Cochrane libraries. The meta-analysis results included genital mycotic infection, related-to-acidosis events, and other related adverse events, including diarrhea, severe nocturnal hypoglycemia event, and volume depletion. In addition, a subgroup analysis was also conducted based on different doses of sotagliflozin. Moreover, the patient-treated years analyzed in the study were 12 weeks, 24 weeks, and 52 weeks, respectively, for type 1 diabetes, and were 12 weeks, 22 weeks, and 52 weeks, respectively, for type 2 diabetes.
RESULTS
The results of this meta-analysis illustrated that sotagliflozin could increase the risk of genital mycotic infection for patients with T1D and T2D (RR: 3.49, 95% Cl: 2.54-4.79, < 0.001; RR: 2.83, 95% Cl: 2.04-3.93, < 0.001; respectively). In addition, the subgroup analysis showed that the drug doses that could increase the risk of genital mycotic infection were 400 mg and 200 mg (RR: 3.63, 95% Cl: 2.46-5.36, < 0.001; RR: 3.21, 95% Cl: 1.84-5.62, < 0.001; respectively) in T1D. Moreover, sotagliflozin could increase the risk of events related to acidosis in the patients of T1D, including acidosis-related adverse events, positively adjudicated diabetic ketoacidosis, acidosis-related event, and diabetic ketoacidosis (RR: 7.49, 95% Cl: 3.20-17.52, < 0.001; RR: 6.05, 95% Cl: 2.56-14.30, < 0.001; RR: 4.83, 95% Cl: 3.13-7.45, < 0.001; RR: 8.12, 95% Cl: 3.06-21.52, p < 0.001; respectively). In the patients of T2D, sotagliflozin could not increase the risk of DKA (RR: 1.30, 95% Cl: 0.34-4.99, p = 0.70). About serious of acidosis-related adverse events, positively adjudicated diabetic ketoacidosis (DKA) and acidosis-related event, the included studies were not reported for T2D patients. As for the other related adverse events, sotagliflozin was found to be a risk factor for diarrhea and volume depletion in T1D patients (RR: 1.44, 95% Cl: 1.09-1.90, p = 0.01; RR: 2.50, 95% Cl: 1.33-4.69, p < 0.01; respectively) and T2D patients (RR: 1.44, 95% Cl: 1.26-1.64, p < 0.001; RR: 1.25, 95% Cl: 1.07-1.45, p < 0.01; respectively).
CONCLUSIONS
This meta-analysis showed that the adverse events of sotagliflozin were tolerable to patients with DM, in terms of the incidence of genital mycotic infection, related-to-acidosis events, diarrhea, volume depletion, and severe nocturnal hypoglycemia events. In addition, the subgroup analysis of sotagliflozin dosage is considered to have great clinical significance for future guidance of sotagliflozin application in patients with DM.
Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diarrhea; Humans; Hypoglycemia; Randomized Controlled Trials as Topic
PubMed: 36225203
DOI: 10.3389/fendo.2022.968478 -
Frontiers in Public Health 2022This study aimed to summarize the clinical characteristics of programmed death receptor 1 (PD-1) inhibitor-associated type 1 diabetes so as to improve the ability of...
OBJECTIVE
This study aimed to summarize the clinical characteristics of programmed death receptor 1 (PD-1) inhibitor-associated type 1 diabetes so as to improve the ability of clinicians to correctly diagnose and treat it.
METHODS
We reported a case of a 70-year-old woman with gastric cancer who developed hyperosmolar hyperglycemic coma during camrelizumab (a PD-1 inhibitor) treatment and was diagnosed with PD-1 inhibitor-associated type 1 diabetes. We conducted a systematic review of 74 case reports of type 1 diabetes associated with PD-1 inhibitor therapy published before June 2022.
RESULTS
The patient developed type 1 diabetes with hyperosmolar hyperglycemic coma after receiving camrelizumab chemotherapy for 6 months (9 cycles). We searched 69 English articles comprising 75 patients, all of whom had been treated with a PD-1 inhibitor (nivolumab or pembrolizumab) and progressed to diabetes after an average of 6.11 (1-28) cycles. Nivolumab combined with ipilimumab (a cytotoxic T lymphocyte-associated protein 4 inhibitor) had the shortest onset (4.47 cycles on average). A total of 76% (57/75) of patients developed diabetic ketoacidosis (DKA) at onset, and 50.67% (38/75) of patients had C-peptide <0.1 ng/mL. Most of the patients were tested for insulin autoantibodies, with a positive rate of 33.33% (23/69); of these, 86.96% (20/23) were tested for glutamate decarboxylase antibody and 46.67% (35/75) were tested for human leukocyte antigen (HLA). HLA-DR4 was the most common type.
CONCLUSIONS
The progression of type 1 diabetes induced by PD-1 inhibitors is relatively rapid. Islet failure often occurs when detected, seriously endangering patients' lives. Patients treated with PD-1 inhibitors should closely monitor their plasma glucose level during treatment to detect, diagnose, and treat diabetes on time.
Topics: Aged; Coma; Diabetes Mellitus, Type 1; Female; Humans; Immune Checkpoint Inhibitors; Nivolumab
PubMed: 35991054
DOI: 10.3389/fpubh.2022.885001 -
Pediatric Research Apr 2023Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes mellitus (T1DM) that has increased during the COVID-19 pandemic. This study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes mellitus (T1DM) that has increased during the COVID-19 pandemic. This study will not only shed light on such life-threatening complications but also be a step to increase the awareness of healthcare providers about such complications in the upcoming pandemic waves and increased dependence on telemedicine. Thus, we aimed to further investigate the increase of DKA in pediatrics.
METHODS
PubMed, Web of Science, and Scopus were broadly searched for studies assessing the incidence of DKA in pediatrics during the COVID-19 pandemic.
RESULTS
Our study included 24 papers with a total of 124,597 children with diabetes. A statistically significant increase occurred in the risk of DKA among newly diagnosed T1DM patients during the pandemic (RR 1.41; 95% CI 1.19, 1.67; p < 0.01; I = 86%), especially in the severe form of DKA (RR 1.66: 95% CI 1.3, 2.11) when compared to before.
CONCLUSION
DKA in newly diagnosed children with T1DM has increased during the pandemic and presented with a severe form. This may reflect that COVID-19 may have contributed not only to the development but also the severity of DKA.
IMPACT
Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) that has increased during the COVID-19 pandemic. Our study included 25 papers with a total of 124,597 children with diabetes. A statistically significant increase occurred in the risk of DKA among newly diagnosed T1DM patients during the pandemic. Our findings reflect that COVID-19 may have an altered presentation in T1DM and can be related to DKA severity.
Topics: Humans; Child; Diabetic Ketoacidosis; Diabetes Mellitus, Type 1; Pandemics; Incidence; Retrospective Studies; COVID-19; Severity of Illness Index
PubMed: 35953513
DOI: 10.1038/s41390-022-02241-2 -
Frontiers in Endocrinology 2022Most patients with type 1 diabetes (T1DM) do not reach the blood glucose goal with treatment of insulin. In our research, we intended to estimate the therapeutic effect... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most patients with type 1 diabetes (T1DM) do not reach the blood glucose goal with treatment of insulin. In our research, we intended to estimate the therapeutic effect and safety of additional different doses of dapagliflozin on insulin treatment in T1DM.
METHODS
We performed direct and indirect network meta-analysis using Bayesian models and graded different dosages of dapagliflozin by mixed therapy contrasts. We retrieved information from the PubMed, Embase, The Cochrane Library, Web of Science, China Biology Medicine (CBM) disc, China National Knowledge Infrastructure (CNKI), Wanfang Data, and WEIPU Data. Our research included randomized controlled trials (RCTs) including T1DM treated with insulin and additional dapagliflozin 5 mg or dapagliflozin 10 mg from January 2012 to June 2021. Thirteen RCTs with 10,701 participants were divided into three groups as below: insulin alone, dapagliflozin 5 mg + insulin, and dapagliflozin 10 mg + insulin.
RESULTS
Dapagliflozin dose-dependently exhibited reductions in glycated hemoglobin (HbA1c), total insulin daily dose (TDD), and body weight. Neither dapagliflozin 5 mg nor 10 mg could induce hypoglycemia or severe hypoglycemia. However, both doses of dapagliflozin increased the incidence of diabetic ketoacidosis (DKA) and genital infection.
CONCLUSIONS
Dapagliflozin 10 mg could achieve a better outcome in efficacy and could not increase the risk of hypoglycemia. Although it may induce a higher risk of DKA and genital infection, there was no significant difference between dapagliflozin 10 mg and 5 mg. Our outcomes indicate that dapagliflozin 10mg has a high reliability of being graded prior as a supplementary treatment to insulin in T1DM.
Topics: Adult; Benzhydryl Compounds; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glucosides; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Network Meta-Analysis
PubMed: 35872994
DOI: 10.3389/fendo.2022.923376 -
Journal of Medical Virology Nov 2022Viral infections may increase the risk of developing type 1 diabetes (T1D), and recent reports suggest that Coronavirus Disease 2019 (COVID-19) might have increased the... (Meta-Analysis)
Meta-Analysis Review
Viral infections may increase the risk of developing type 1 diabetes (T1D), and recent reports suggest that Coronavirus Disease 2019 (COVID-19) might have increased the incidence of pediatric T1D and/or diabetic ketoacidosis (DKA). Therefore, this meta-analysis aims to estimate the risk of global pediatric new-onset T1D, DKA, and severe DKA before and after the COVID-19 pandemic. A systematic search of MEDLINE/PubMed, CINAHL, Scopus, and EMBASE was conducted for articles published up to March 2022. A random-effects meta-analysis was performed to compare the relative risk of T1D and DKA among pediatric patients with T1D between the COVID-19 pre-pandemic and pandemic periods. We also compared glucose and HbA1c values in children who were newly diagnosed with T1D before and after the COVID-19 pandemic. The global incidence rate of T1D in the 2019 period was 19.73 per 100 000 children and 32.39 per 100 000 in the 2020 period. Compared with pre-COVID-19 pandemic, the number of worldwide pediatric new-onset T1D, DKA, and severe DKA during the first year of the COVID-19 pandemic increased by 9.5%, 25%, and 19.5%, respectively. Compared with pre-COVID-19 pandemic levels, the median glucose, and HbA1c values in newly diagnosed T1D children after the COVID-19 pandemic increased by 6.43% and 6.42%, respectively. The COVID-19 pandemic has significantly increased the risk of global pediatric new-onset T1D, DKA, and severe DKA. Moreover, higher glucose and HbA1c values in newly diagnosed T1D children after the COVID-19 pandemic mandates targeted measures to raise public and physician awareness.
Topics: COVID-19; Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glucose; Glycated Hemoglobin; Humans; Incidence; Pandemics
PubMed: 35831242
DOI: 10.1002/jmv.27996 -
Computational and Mathematical Methods... 2022To evaluate the effectiveness of different glucose monitoring methods on blood glucose control and the incidence of adverse events among patients with type 1 diabetes... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the effectiveness of different glucose monitoring methods on blood glucose control and the incidence of adverse events among patients with type 1 diabetes mellitus.
METHODS
Using the method of literature review, the databases PubMed, Cochrane, and Embase were retrieved to obtain relevant research literature, and the selected studies were analyzed and evaluated. This study used Cochrane software RevMan5.4 to statistically analyze all the data.
RESULTS
A total of 15 studies were included in this study, including 10 randomized controlled trials and 5 crossover design trials, with a total of 2071 patients. Meta-analysis results showed that continuous blood glucose monitoring (CGM) could significantly reduce the HbA1c level of patients, weighted mean difference (WMD) = -2.69, 95% confidence interval (CI) (-4.25, -1.14), and < 0.001 compared with self-monitoring of blood glucose (SMBG). Meanwhile, the incidence of severe hypoglycemia in the CGM group was significantly decreased, risk ratio (RR) = 0.52, 95% CI 0.35-0.77, and = 0.001. However, there was no statistical difference in the probability of diabetic ketoacidosis between CGM and SMBG groups, RR = 1.34, 95% CI 0.57-3.15, and = 0.5.
CONCLUSION
Continuous blood glucose monitoring is associated with lower blood glucose levels than the traditional blood glucose self-test method.
Topics: Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Glucose; Humans; Hypoglycemia; Randomized Controlled Trials as Topic
PubMed: 35761839
DOI: 10.1155/2022/2851572 -
Globalization and Health Jun 2022Apart from infecting a large number of people around the world and causing the death of many people, the COVID-19 pandemic seems to have changed the healthcare processes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Apart from infecting a large number of people around the world and causing the death of many people, the COVID-19 pandemic seems to have changed the healthcare processes of other diseases by changing the allocation of health resources and changing people's access or intention to healthcare systems.
OBJECTIVE
To compare the incidence of endpoints marking delayed healthcare seeking in medical emergencies, before and during the pandemic.
METHODS
Based on a PICO model, medical emergency conditions that need timely intervention was selected to be evaluated as separate panels. In a systematic literature review, PubMed was quarried for each panel for studies comparing the incidence of various medical emergencies before and during the COVID-19 pandemic. Markers of failure/disruption of treatment due to delayed referral were included in the meta-analysis for each panel.
RESULT
There was a statistically significant increased pooled median time of symptom onset to admission of the acute coronary syndrome (ACS) patients; an increased rate of vasospasm of aneurismal subarachnoid hemorrhage; and perforation rate in acute appendicitis; diabetic ketoacidosis presentation rate among Type 1 Diabetes Mellitus patients; and rate of orchiectomy among testicular torsion patients in comparison of pre-COVID-19 with COVID-19 cohorts; while there were no significant changes in the event rate of ruptured ectopic pregnancy and median time of symptom onset to admission in the cerebrovascular accident (CVA) patients.
CONCLUSIONS
COVID-19 has largely disrupted the referral of patients for emergency medical care and patient-related delayed care should be addressed as a major health threat.
Topics: COVID-19; Delivery of Health Care; Emergencies; Humans; Pandemics; Retrospective Studies; SARS-CoV-2
PubMed: 35676714
DOI: 10.1186/s12992-022-00836-2 -
Diabetes, Obesity & Metabolism Sep 2022To identify, appraise and synthesize the available evidence on the impact of the coronavirus disease 2019 (COVID-19) pandemic and lockdown (LD) on glycaemic control in... (Meta-Analysis)
Meta-Analysis
AIM
To identify, appraise and synthesize the available evidence on the impact of the coronavirus disease 2019 (COVID-19) pandemic and lockdown (LD) on glycaemic control in people with diabetes.
MATERIALS AND METHODS
We searched multiple databases up to 2 February 2021 for studies reporting HbA1c, time in range (TIR), average or fasting glucose, severe hypoglycaemia and diabetic ketoacidosis. Data were pooled using random effects meta-analysis and are presented as mean difference (MD) with 95% confidence intervals (CI). This review was preregistered on PROSPERO (CRD42020179319).
RESULTS
We include 59 studies; 44 (n = 15 464) were included in quantitative syntheses and 15 were narratively synthesized. Pooled data were grouped by diabetes type. Results from 28 studies (n = 5048 type 1 diabetes [T1D] and combined diabetes participants) showed that TIR increased during LD compared with before LD (MD 2.74%, 95% CI 1.80% to 3.69%). Data from 10 studies (n = 1294 T1D participants) showed that TIR increased after LD compared with before LD (MD 5.14%, 95% CI 3.12% to 7.16%). Pooled results from 12 studies (n = 4810 T1D and type 2 diabetes participants) resulted in average glucose decreasing after LD compared with before LD (MD -6.86 mg/dl, 95% CI -8.54 to -5.18). Results for other outcomes, including HbA1c, were not statistically significantly different.
CONCLUSIONS
The COVID-19 pandemic was associated with small improvements across multiple outcomes of glycaemic control, although there was insufficient evidence to suggest that this led to changes in HbA1c. Most evidence came from people with access to diabetes technologies in high-income countries; more research is needed in less advantaged populations.
Topics: COVID-19; Communicable Disease Control; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glucose; Glycated Hemoglobin; Glycemic Control; Humans; Pandemics
PubMed: 35603919
DOI: 10.1111/dom.14771